DEMONSTRATION OF FUNCTIONAL SIMILARITY OF PROPOSED BIOSIMILAR ABP 798 TO RITUXIMAB
(Abstract release date: 05/18/17)
EHA Library. McBride H. 05/18/17; 182563; PB1849
Helen McBride
Contributions
Contributions
Abstract
Abstract: PB1849
Type: Publication Only
Background
Proposed biosimilars undergo comprehensive structural and functional characterization before they can be studied in confirmatory clinical trials. ABP 798 is being developed as a biosimilar to rituximab. The originator is approved for treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, severe rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.
Aims
ABP 798 was compared with rituximab sourced from the European Union (EU). Quality attributes assessed included binding properties (CD20, C1q, FcRn, and Fcγ receptors), antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and induction of apoptosis.
Methods
Binding of ABP 798 and rituximab to the CD20 antigen was characterized using a cell-based CD20 binding assay utilizing the human B-lymphoblastoid, WIL2-S, cell line. A direct binding ELISA was used to assess the binding of the Fc domain of ABP 798 to C1q. Binding of the Fc moiety of ABP 798 and rituximab to FcγRIa, FcγRIIa, FcγRIIb, and FcγRIIIa (158V) were evaluated in AlphaLISA® competitive binding assays. Binding to FcRn was evaluated by an AlphaScreen® competitive binding assay. ADCC activity was evaluated in a functional cell-based assay, with CD20-expressing WIL2-S cells used as target cells and NK92-M1 cells, stably transfected with human CD16 (FcγRIIIa [158V]), used as effector cells. CDC activity was evaluated in a functional cell-based assay using a CD20 expressing human B-lymphoblastoid WIL2-S cell line and baby rabbit complement. Induction of apoptosis was assessed by measuring activation of caspase 3/7 in SU-DHL-4 cells, a CD20-expressing human B cell lymphoma cell line.
Results
Relative binding (%) was comparable between ABP 798 and rituximab (Table).
Assay | ABP 798 | Rituximab |
CD20 | 91 – 105 | 82 – 105 |
C1q | 85 – 100 | 85 – 89 |
FcRn | 89 – 104 | 92 – 115 |
FcγRIa | 94 – 98 | 87 – 95 |
FcγRIIa | 96 – 102 | 96 – 106 |
FcγRIIb | 96 – 108 | 93 – 109 |
FcγRIIIa (158V) | 88 – 100 | 67 – 97 |
The dose response profiles and relative activity for ADCC and CDC were similar (mean ADCC relative activity: ABP 798, 88%; rituximab, 86%; mean CDC relative potency: ABP 798, 103%; rituximab, 104%). The dose response profile for induction of caspase 3/7 was comparable between ABP 798 and rituximab.
Conclusion
The results presented here suggest that ABP 798 is similar to rituximab sourced in the EU in terms of biological activity across the range of tested functions. These results provide a firm foundation for further clinical development of ABP 798.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): antibody, Rituximab, Immunotherapy
Abstract: PB1849
Type: Publication Only
Background
Proposed biosimilars undergo comprehensive structural and functional characterization before they can be studied in confirmatory clinical trials. ABP 798 is being developed as a biosimilar to rituximab. The originator is approved for treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, severe rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.
Aims
ABP 798 was compared with rituximab sourced from the European Union (EU). Quality attributes assessed included binding properties (CD20, C1q, FcRn, and Fcγ receptors), antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and induction of apoptosis.
Methods
Binding of ABP 798 and rituximab to the CD20 antigen was characterized using a cell-based CD20 binding assay utilizing the human B-lymphoblastoid, WIL2-S, cell line. A direct binding ELISA was used to assess the binding of the Fc domain of ABP 798 to C1q. Binding of the Fc moiety of ABP 798 and rituximab to FcγRIa, FcγRIIa, FcγRIIb, and FcγRIIIa (158V) were evaluated in AlphaLISA® competitive binding assays. Binding to FcRn was evaluated by an AlphaScreen® competitive binding assay. ADCC activity was evaluated in a functional cell-based assay, with CD20-expressing WIL2-S cells used as target cells and NK92-M1 cells, stably transfected with human CD16 (FcγRIIIa [158V]), used as effector cells. CDC activity was evaluated in a functional cell-based assay using a CD20 expressing human B-lymphoblastoid WIL2-S cell line and baby rabbit complement. Induction of apoptosis was assessed by measuring activation of caspase 3/7 in SU-DHL-4 cells, a CD20-expressing human B cell lymphoma cell line.
Results
Relative binding (%) was comparable between ABP 798 and rituximab (Table).
Assay | ABP 798 | Rituximab |
CD20 | 91 – 105 | 82 – 105 |
C1q | 85 – 100 | 85 – 89 |
FcRn | 89 – 104 | 92 – 115 |
FcγRIa | 94 – 98 | 87 – 95 |
FcγRIIa | 96 – 102 | 96 – 106 |
FcγRIIb | 96 – 108 | 93 – 109 |
FcγRIIIa (158V) | 88 – 100 | 67 – 97 |
The dose response profiles and relative activity for ADCC and CDC were similar (mean ADCC relative activity: ABP 798, 88%; rituximab, 86%; mean CDC relative potency: ABP 798, 103%; rituximab, 104%). The dose response profile for induction of caspase 3/7 was comparable between ABP 798 and rituximab.
Conclusion
The results presented here suggest that ABP 798 is similar to rituximab sourced in the EU in terms of biological activity across the range of tested functions. These results provide a firm foundation for further clinical development of ABP 798.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): antibody, Rituximab, Immunotherapy
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